Lineage Cell Therapeutics, Inc.

Welcome to the Lineage Style Therapeutics Third Quarter 2023 Conference Call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available on the Investors section of Lineage's website at .lineagestyle.com. This call is subject to copyright and is the property of Lineage. And recordings, reproductions, or transmissions of this call without the expressed written consent of Lineage are strictly prohibited. As a reminder, today's call is being recorded. I would now like to introduce your host for today's call, Iwona Hone, Head of Investor Relations at Lineage. Ms. Hone, please go ahead.

Thank you, Jordan. Good afternoon and thank you for joining us. A press release reporting our Third Quarter 2023 financial results was issued earlier November 9, 2023 and can be found on the Investors section of our website. Please note that today's remarks and responses to your questions reflect management's views as of today only and will contain forward-looking statements within the meaning of federal securities laws. Statements made during this discussion that are not statements of historical fact should be considered forward-looking statements, which are subject to significant risks and uncertainties. The company's actual results or performance may differ materially from the expectations indicated by such forward-looking statements. For a discussion of certain factors that could cause the company's results or performance to differ, we refer you to the forward-looking statements sections in today's press release and in the company's SEC filings, including its most recent annual report on Form 10-K and its subsequent quarterly reports on Form 10-Q. We caution you not to place undue reliance on any forward-looking statements, which speak only as of today and are qualified by the cautionary statements and risk factors described in our SEC filings. With us today are Brian Culley, our Chief Executive Officer, Jill Howe, our Chief Financial Officer, and Gary Hogue, our Senior Vice President of Clinical and Medical Affairs. With that, I'd like to turn the call over to Brian.

Thank you, Iwona. Good afternoon, everyone. We appreciate you taking the time to join us today. I'm pleased to report that everything remains on track with our most important development plans and we continue to have many reasons to be excited about the future. For example, we recently reached a milestone with the ANP-1 program for hearing loss, which I look forward to describing further today. But first, I want to start off by talking about our manufacturing subsidiary because it is located in Israel and the work performed by that group is very important to us. We have more than 50 employees in Israel and naturally, the safety and well-being of that team is our top priority. Fortunately, there has been almost no impact on our operations due to the Israel-Hamas war. Our facility itself is located in a suburban area, approximately 30 minutes outside of and it has not been directly impacted by the ongoing conflict. We have an extremely capable and dedicated team and while a small number of employees or spouses were called up for reserve duty, the team has continued to maintain their high level of output, in particular, by completing the final validation work for OPC-1 and continuing manufacturing activities for OPERGYN. As additional support for our employees, we have made supplemental employee services available as may be needed. And in the meantime, we will continue to monitor the situation closely and if needed, we will adjust our operations accordingly, but we expect we will be able to continue to operate our business as normal in both Israel and the U.S. Moving on to OPERGYN, we were pleased to present last week at the Icelerator conference in San Francisco in a session called Mapping the Future of Geographic Atrophy. There were more than 40 ophthalmology companies showcasing their innovations, but we were one of just four companies selected to share the main stage with Apelis and Iverick Estellis in front of a large audience of retinal specialists, investors and other interested parties. It was wonderful to be recognized among the most promising approaches in the GA space and I hope the replay from that presentation will be available soon for your review. As an additional part of our ongoing efforts to broaden awareness of the OPERGYN program, Roch and Genentech electively reported data last month from our Phase 1-2a clinical study at the 23rd EU Retina Congress. These latest results, which were independently generated and reported by our partners, focused on the rapid time to onset of retinal structure improvements in OPERGYN treated patients, which are vastly faster than anti-compliment approaches. You may have noticed that there has been a lot of attention recently drawn to the effects of complement inhibition during its third consecutive year of treatment or as I prefer to call it after 18 to 36 injections. Meanwhile, our data showed that after just a single administration of OPERGYN, improvements to retinal structure were detectable in some cases just days later and always within three months. As a reminder, all five patients who had extensive coverage of the GA lesion with the surgical bleb containing a suspension of OPERGYN demonstrated evidence of improvement in outer retinal structure and visual acuity gains at 12 months. Additionally, maintenance or greater improvements in retinal structure were observed over time. These data continue to give us confidence in our lead asset and we look forward to additional future clinical data updates on the OPERGYN program from our partners Roch and Genentech for both the fully enrolled Phase 1-2a study, which we conducted, as well as from Roch's Phase 2a study, which is currently enrolling. In parallel with these additional data announcements, we have continued inventing and patenting new process development methods to support long periods of exclusivity for our pipeline of cell transplant programs, including OPERGYN. In September, the USPTO issued a patent entitled Large Scale Production of Retinal Pigment Epithelial Cells. This patent, which has been exclusively licensed to lineage, has an expected expiration date of July 28, 2036 and we believe further enhances the value of the OPERGYN program. For reasons I've shared previously on several occasions, I'm unfortunately not yet able to provide any details about the results from the ongoing Phase 2a trial of OPERGYN. But patient enrollment continues, data are being collected and additional sites are expected to come online, which you can follow at clinicaltrials.gov. And while I'm not able to speak to when or where top line data will be available, we understand that investors are eager to learn whether Roch can reproduce the clinical observations which lineage reported from our Phase 1-2a study and we aim to provide that information at our first possible opportunity. Moving next to OPC-1, our spinal cord program, we remain on track to submit the IND amendment for the new delivery device before year end. The work we have been conducting recently is necessary to submit the IND amendment, which itself is a requirement to initiate our planned clinical safety study of the new spinal cord delivery device, which we licensed from NeurGAME Technologies. Assuming submission of the INDA before year end as we've planned and if no FDA comments are received in the 30 days following that submission, that will permit us to bring OPC-1 back into clinical testing by opening our first site and initiating this small safety study in subacute and chronic patients with either thoracic or cervical spinal cord injuries, presumably in Q1 of next year. In parallel with this work, we continue to be in contact with the California Institute for Regenerative Medicine regarding potential financial support for the OPC-1 program and specifically for this anticipated clinical trial. As I've shared before, we intend to apply for financial support for this study after we complete the 30 day waiting period or address any further requirements for our IND amendment as is consistent with CIRM guidelines. Moving next to ANP-1, we committed to providing an update before year end and I'm happy to provide that update today. As a reminder, ANP-1 is our cell transplant program being developed to address hearing loss and we have been conducting preclinical testing of our ANP-1 cells through a collaboration with the University of Michigan. Our initial objectives from this collaboration were to evaluate the delivery of our cells into specific target areas using standard surgical tools, to monitor initial engraftment of our cells into certain anatomical destinations and to assess whether our cells survive after transplantation. We also wanted to see whether the cells migrated and if they were expressing certain markers of neuronal identity. The outcomes from this initial proof of concept work were both positive and encouraging and we consider the results sufficient to advance this program into its next phase of preclinical development, which is to evaluate our ANP-1 cells in a functional model of hearing loss. Two reasons why we're excited about reaching this milestone and proceeding into functional assessments are first, the recent deal activity in the hearing loss space, which includes early stage assets and second, clinical reports from gene therapy approaches to treat certain kinds of hearing loss. We believe cell therapy may have advantages over certain kinds of gene therapy insofar as replacing the entire cell means you don't have to select for patients who carry a specific genetic defect. We think this offers cell therapy larger addressable markets while matching the advantages of the one and done treatment schedule of gene therapy. And if we're able to demonstrate a functional signal in an animal model, that may create opportunities for business development or partnering of ANP-1 if we determine that's the preferred path for us to pursue. I am also excited about the ANP-1 program because it represents our flagship example of the speed and return on R&D investment which is possible with the lineage platform. We advanced from little more than a product concept into preclinical testing in less than 12 months and with an initial investment of less than $1 million. That is possible largely because the pluripotent cell lines which we start with are by definition capable of differentiating into every cell type of the human body. Once we figure out how to make the desired cell and can do so in a reproducible and scalable manner we have essentially created a new pipeline asset. And while clearly this is an environment where capital raising is not cooperating with opportunities for rapid expansion, we will continue to try to find clever and affordable ways to extend our capabilities and unlock value in the months and years ahead. As a second example of our efforts to create significant long-term value without large capital commitments, during this past quarter we initiated certain development activities under our partnership with Eterna Therapeutics. This collaboration with Eterna is an example of our strategy of capitalizing on our extensive and proprietary process development capabilities by combining them with externally accessed cell engineering and cell editing technologies all for the purpose of creating novel and potentially superior product candidates. In the specific case of Eterna we finalized the selection of edits for the initial IPSC cell lines being developed to reduce the immunogenicity of certain product candidates and we additionally selected a particular edit intended to confer clinical differentiation and a competitive advantage in its applicable indication. And while we believe it is premature to disclose this program at this time, if we do reach predefined developmental milestones next year we will look forward to sharing more details on this initiative with you. To wrap up, the biotech environment continues to be extraordinarily challenging. The sector is experiencing historic underperformance and in some cases even what appears to be positive news isn't being rewarded. But regardless, I believe lineage continues to be well positioned to advance our business. Our commitment to financial discipline has helped us remain relatively stable for the past two years. And do I wish we could move faster? Of course. But capital comes with a cost and sometimes it's better to reduce your pace of investment such as when we made the strategic decision to divert the VAC2 program to more of a BD project instead of initiating a clinical study on our own. But the most important thing overall is that we've been able to keep moving forward in these difficult times. And I think our progress is demonstrated in our frequent business updates. And with our lead asset being advanced by Roche and Genentech, we believe lineage can offer shareholders an opportunity to reset expectations about what is possible in the treatment of geographic atrophy which continues to represent an unmet need despite recent marketing authorizations from competing agents. So to summarize the three key points for today, one, the events in Israel have not had a material impact on our business. Two, we continue to be extremely happy with the relationship we have with Roche and Genentech including their commitment to advancing OPERGYN. And three, we are eager to complete the final steps for the OPC1 IND amendment this year so that we can have a second cell transplant program in active clinical development. And with that, I will hand the call to Jill for a discussion of our financials.

Thanks Brian and good afternoon everyone. Beginning with our balance sheet, I'm pleased to report that we continue to be well capitalized to conduct this near-term activity which Brian just outlined. Our reported cash, cash equivalents and marketable securities as of September 30, 2023 totaled $41.3 million which is expected to support our current planned operations into the first quarter of 2025. This is one quarter further than some of you may have expected and is due to efficiencies and opportunities to extend our runway which we have identified during the quarter and which we will continue to look for going forward. Next, we will review our third quarter operating results. Our revenue is generated primarily from licensing fees, royalties, collaboration revenues and research grants. Total revenues for $1.2 million, a net decrease of $1.8 million as compared to approximately $3 million for the same period in 2022. The decrease is primarily driven by lower collaboration and licensing revenues recognized from deferred revenues from the Roche agreement. Operating expenses are comprised of research and development expenses and general and administrative expenses. Total operating expenses are $7.8 million, a decrease of $0.2 million as compared to $8 million for the same period in 2022. R&D expenses were $3.7 million, a net increase of $0.1 million as compared to $3.6 million for the same period in 2022. The net increase is primarily driven by $0.2 million in higher OPC-1 program related expenses and $0.5 million in expenses to support preclinical and other research and development programs. These increases were primarily offset by a $0.5 million decrease in our VAC program, primarily related to reduce manufacturing activities. G&A expenses were $4 million, a net decrease of approximately $0.4 million as compared to $4.4 million for the same period in 2022. The decrease is primarily due to an overall reduction in costs incurred for services by third parties, consulting costs, and recruiting related expenses. Laws from operations were $6.7 million, an increase of $1.5 million as compared to $5.2 million for the same period in 2022. As a reminder, this loss was driven by a non-cash expense, primarily due to revenue recognition associated with the Roche agreement. Other income and expenses included other expenses of $0.4 million compared to other expenses of $0.3 million for the same period in 2022. The change was primarily driven by exchange rate fluctuations related to our international subsidiaries, fair market value changes in marketable equity securities, and interest income from our marketable debt securities. The net loss was $7.1 million or $0.04 per share compared to a net loss of $6.1 million or $0.04 per share for the same period in 2022. Overall, we have maintained our same spending discipline which continues to serve as well. As the uncertainty impacting the biotech market continues, we believe that maintaining discipline in our spending will continue to allow us to maintain our plan to reach meaningful milestones, make important progress, and create value for shareholders from our investments in our programs. Now let me hand the call back to Brian.

Great, thanks Jill. As I said at the accelerator conference last week, cell therapy has revolutionized the oncology world. Cell therapy stands alongside chemotherapy and surgery as one of the pillars of cancer therapy, and we believe that cell therapy and the cell therapy revolution will extend beyond oncology into other areas, including ophthalmology, and we'll continue to strive to apply differentiated cells in a replace and restore approach to help achieve that end. A key piece of that journey and presumably one of the biggest questions for potential lineage investors is whether Roche will be able to independently reproduce our findings of improved retinal structure and function with Oprigen. So we'll be doing everything we can to support their efforts to conduct the ongoing study while also working closely with them to transfer our production process to their manufacturing facility in the US, which will help support any further development and commercialization activities which are pursued. I appreciate your attention today, and with that, operator, we are ready to take analysts' questions.

Thank you. Your first question comes from the line of Joseph Han-Genis from HC Wrenright. Your line is live.

Hey, everybody. Good afternoon. Thanks for taking the question. So, Brian, I'm going to ask about the Oprigen Phase 2A anyway, but I'm going to ask it this way. Based on the totality of the data and especially the recent imaging data, do you have any sort of anecdotal comments how this may have impacted positively the conduct of the study and being able to, say, bring on principal investigators or additional sites quicker?

Thank you for the question, Joe. My response won't have any specific anecdotal references. What I will reference is a previous statement I made on a call like this where I said that I felt that the first, I don't know, let's say, dozen or so people who underwent this therapy were incredibly courageous and brave. They were the first in the world. Now that we have been able to show the kinds of clinical outcomes which are possible, my response is that the investigative site and the patient could be easier because they can point to some of the same data which Roshan Genentech has been presenting through their channels or which lineage previously presented through its own channels. But I do want to emphasize that that is not a specific statement over the conduct of the ongoing Phase 2. That's entirely under the control of Roshan Genentech. I just think that the fear factor could be mitigated in part by some of the wonderful outcomes that we have described previously.

That's totally fair. I appreciate that. And then if we just go down a little earlier into the pipeline, you made some ANP1 comments today, whether it's that asset or others, when do you think we might be able to see, say, preclinical data in a poster or some other fashion and separately as part of the earlier stage assets, how would you describe the current interest with regard to the VAC platform? Thanks a lot.

Yeah, thank you also for that question. My mind turns to what I described a moment ago which is a functional preclinical model with ANP1. I don't think that I would want to wait for some sort of research conference if we generated encouraging data in that setting because while the initial proof of concept work that we did around delivery, migration, expression of identity factors, that's important and even necessary, I think the true inflection point, the early stage inflection point for a program like ANP1 is some sort of indication of functional effect in an animal model because that has been largely elusive to different approaches to date. So we, as I described, we are designing that next phase of preclinical development right now. We intend to conduct that through the alliance we already established with the University of Michigan, but these studies do take months to conduct and quality check and so forth. So certainly a 2024 event, not a 2023 event, but I think that would be the one that I think would be quite exciting in part because of the considerable addressable market for hearing loss as well as some of what I referenced earlier which are the BDE activity in hearing loss has been quite substantial even for early stage assets.

And VAC platform interest?

Yes, VAC is continuing to be a project for the business development team rather than internal clinical development program, again in part due to some, let's say, partial rationalization of the biotech environment and then also because of the nature of the VAC program, i.e. that different antigens could be presented through the dendritic cell and it is impossible to think that we could exhaust all of the different product profiles that one could contemplate using that. So we very much see that more as a mini platform which is more well suited to try to develop through partnership activity rather than with our own current capital on hand.

Thank you. Thank you, Joe.

Your next question comes from the line of Jack Allen from RW Baird. Your line is live.

Hi, this is Abby on for Jack. On the updates as it relates to the Aterna partnership and development of hypoimmune cells for neurological indication, we are hoping you might be able to provide some additional color surrounding what sorts of indications you might be going at in neurology and what drove you to this.

Thank you, Abby, for that question. I think it is comfortable to say that a hypoimmune cell line offers some potential advantages in indications where rejection is of greater concern than in the eye or in the spinal cord. That is not to say that a hypoimmune line couldn't still be utilized in places that are immunoprivileged, but that is not necessarily what we have in mind in trying to generate that line. I don't think at this point we are at a position to say anything more than there are indications that might be good opportunities for a cell transplant approach for which having a hypoimmune line makes a lot of sense. I can obviously point to what people have seen in type 1 diabetes and I think some of the NHP data, non-human primate data coming out of a similar company down the road from us, I think is quite evocative. So this is part of a larger strategy of utilizing and relying on our process development expertise and thinking about where this technology will go because I find it difficult to imagine that the only place we can get these extraordinary clinical outcomes is in the setting of the eye and even specifically utilizing RPE. I think that this field will reveal itself to have and harbor other opportunities, but they might be more easily addressed using a hypoimmune line than a line where you have risks of rejection. I should probably note that we have approximately 100 person years of exposure of our non-hypoimmune lines with operagen and we have never had a single case of rejection. That's not to say that it is a non-zero possibility. This is biology and it is complex, but our approach here is to have staged investment from the later stage such as the Phase II program with operagen all the way back to very early stage cell line development which is what we are doing via the alliance with Eterna which by the way also includes more of a strategic gene edit that has a very specific purpose in an as yet undisclosed indication.

Wonderful, thank you. And then as a follow-up, you had mentioned Type 1 diabetes. I was wondering if you could kind of comment on your thoughts about the initial proof of concept as it relates to Bayer slash Blue Rocks program in Parkinson's.

I love it. I think that it helps to validate a replace and restore strategy. I'm encouraged by what I've seen. I must acknowledge that I'm not an expert in Type 1 diabetes. Our company as you know is much more neurologically oriented, but I do think that the mechanistic principles which underlie their work and our work share a lot of common features and that is exactly why we are looking for affordable ways to expand the scope of our platform and how it gets deployed.

Wonderful, thank you so much. Thank you, Abby.

Your next question comes from the line of Kristin Kloska from Cancer Fitzgerald. Your line is live.

Hi, good afternoon everybody. Thanks for taking my question. I wanted to ask if you're aware or seeing any new trends as it relates to enrollment in general, not specifically asking you to comment on Oprigen in light of some of the advances we've seen over the last few months. So on one hand, there are therapies available now, but then on the other hand, perhaps those that were excited to try these may be looking for other options given some of the safety issues that have come up.

Kristin, if I could ask you to expand a little on that. My mind is thinking about when COVID first came along and people on ophthalmology clinical trials began skipping appointments for, for example, wet AMD therapies, but is that what you have in mind or something more specific to Oprigen?

Just like the geographic atrophy space in general, meaning that, you know, there are therapies approved now. So on one hand, patients may not be as interested in a clinical trial, but then to play devil's advocate here, maybe those patients that were interested in getting on an approved therapy might be having second thoughts in light of the safety issues that have arised.

Thank you. My personal experience, because I'm not collecting data that one can rely on, but I sit there and I see the commercials for the approved agents just like all of us. And because of my association with GA, I also monitor some of the issues and concerns around vasculitis or other AEs. I believe what that all points to is the unavoidable relationship between the clinical benefit and the safety profile of any asset. And I think that the reason that safety has become the focus of the anti-complement field of late is attributable to the fact that there are some real questions, not about the rate of AE and the risk to the patient, but whether the benefits are worth taking that risk. So to put a finer point on it, you just don't get very much clinical benefit to justify the risks of even rare adverse events. I think that is contrasted with the current product profile of Oprigen or the desired product profile of Oprigen insofar as we are going to great lengths to point to visual gains, not slower losses, and the improvement in retinal architecture rather than slowing the progression of the disease. So we are talking about clinical outcomes that are wildly beyond the reach of anti-complement, and that would naturally invite a different level of tolerability on adverse events. These ultimately all feed down to individual choice. There are people who are willing to go to great lengths and take great risks because vision is so critical to their daily living. There are others that feel quite differently. So I don't think that there is a unanimous perspective with respect to patient population, but I do think that the patient population is getting increasingly educated thanks to the approval of the anti-complement therapies, because whereas in the past they were told, I can't do anything for you, stop smoking and eat your leafy green vegetables, now they are becoming experts on their condition and they are understanding these tradeoffs and these risks. I think the overall competitive landscape and the commercial opportunity is very favorable for Oprigen because I think that the clinical benefits are compelling. I think a single procedure is very compelling with respect to compliance and follow-up, and I am hopeful that ultimately the safety profile of Oprigen will also provide a better ratio compared to what we are seeing on almost a daily basis with anti-complement. I hope that is helpful to provide my view of that question.

No, it is. Thanks so much. And then can you remind us or share what your latest thoughts are around the market opportunity specific for spinal cord injury? I know you've done a lot of work with your peers in the space in particular to really put your heads together and think about a number of these questions. Thanks so much.

Thank you for that question, Kristen. Because the company neither prices its product candidate at this point nor have we got a definitive idea as to what would be an on-label patient population, it would be difficult to say what we think a peak sales, for example, of that asset would be. What we can point to are some reference information. Globally, the overall spinal cord therapy market, I believe, is referenced upwards of $7, $8, $9, $10 billion. I think that Neuralink, which is the Elon Musk company, recently provided some very specific projections about what they think their pricing could be and how many patients they think they could be treating, I believe, in year five. I think they kind of came out somewhere around $800 million U.S. dollars. So there are some data points out there. For us, we haven't refined it beyond our internal analyses simply because it still is early and it will be driven, of course, by value-based pricing. So we don't know what it's worth, so to speak, because we don't have a real strong metric to use. But that is actually part of the clinical study design is to ensure that we are tracking and measuring things that are important to patients so that we can justify a high value in connection with the pricing of any future therapeutic which gets approved. So there's a tremendous unmet need. There are a lot of different approaches out there. Certainly, we feel comfortable that it is worth the investment in the space. There is a paucity of competing programs, and our approach could work quite comfortably with a lot of other approaches, such as electrical stimulation or some of the more physical, external, mechanistic approaches that are being developed, including potentially some of the brain interface work that is starting to emerge as really interesting as well. So I'm sorry I can't keep it short and just give you a number, but we feel comfortable that it merits continued investment because it does represent an exciting area that, again, can cooperate with other approaches that are in development.

Thanks a lot, Brian. Thank you, Kristen.

Your final question comes from the line of Mayank Mampany from B. Riley Security. Your line is live.

Hey, guys. Madison here from Mayank. A couple of questions from me. One, you mentioned you guys are looking at clever financing, and then I believe you said that in regards to Eterna, there are some predefined milestones next year. So I'm just wondering if I heard that correctly, and if so, if you could mention what kind of the trigger is, what is the kind of threshold there that you would need to hit. And then secondly, the A&P 1 functional model, I'm wondering if that's a model that you guys have created or are creating or if it's a widely used model in the literature. And then lastly, if you could tell us the transfer of activities to Roach for manufacturing, kind of the status of that. I know it's still ongoing, but if you could kind of mention the progress made, say, versus last quarter. Thanks, guys.

Yeah, thank you, Madison. Hopefully I tracked those questions correctly. With respect to clinical financing, you know, we're fortunate that we believe that our programs, and in particular the OPC-1 spinal cord program, are a good match for the California Institute for Regenerative Medicine, and we would hope to be eligible for and receive financial support. I would suggest to you that I'm not sure that there is a better cost of capital than that fantastic program that is available here in the great state of California. So I really like CIRM and I'm hopeful we'll be able to get support as that program has received support in the past. And I know of no reason we wouldn't be eligible in the future. With respect to ETERNA and TRIGGERS, the agreement that we have is one in which there are certain performance metrics which ETERNA is looking to accomplish in generating the line. So we are funding a certain amount of work and they are going to produce a deliverable, and that deliverable has to meet certain criteria. If it does, that would trigger some elective payments if we want to continue, and we want to continue. That would be success. But if they fail, we are not compelled to have to continue. But we elected previously that we would be making some investment in their work and supporting some of that work almost like an outsource model because we are not gene editing experts and do not have those capabilities here. Your third question around ANP1 and the model, actually let me finally bring in Dr. Hogue and he can talk about whether we're looking for precedent. And then Gary, you may as well continue on tech transfer, although there's little we're allowed to say.

Hey Madison. So we're working with a group in Michigan and a number of other groups. There are a number of well-known models and outcome assessments. So the intention is not to develop something de novo, but to utilize that as precedent. And so we're working with those groups to figure out the best models for that. But we're not reinventing the wheel here. And as Brian alluded to, the tech transfer is on target at this point. That's not all we can say.

Got it. Appreciate it, guys. There are no further questions at

this time. That concludes our meeting for today. You may now disconnect from the conference. Thank you, Jordan. Bye, everyone.